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Although replication proteins are conserved among eukaryotes, the sequence requirements for replication initiation differ between species. In all species, however, replication origins fire asynchronously throughout S phase. The temporal program of origin firing is reproducible in cell populations but largely probabilistic at the single-cell level. The mechanisms and the significance of this program are unclear. Replication timing has been correlated with gene activity in metazoans but not in yeast. One potential role for a temporal regulation of origin firing is to minimize fluctuations in replication end time and avoid persistence of unreplicated DNA in mitosis. Here, we have extracted the population-averaged temporal profiles of replication initiation rates for S. cerevisiae, S. pombe, D. melanogaster, X. laevis and H. sapiens from genome-wide replication timing and DNA combing data. All the profiles have a strikingly similar shape, increasing during the first half of S phase then decreasing before its end. A previously proposed minimal model of stochastic initiation modulated by accumulation of a recyclable, limiting replication-fork factor and fork-promoted initiation of new origins, quantitatively described the observed profiles without requiring new implementations.The selective pressure for timely completion of genome replication and optimal usage of replication proteins that must be imported into the cell nucleus can explain the generic shape of the profiles. We have identified a universal behavior of eukaryotic replication initiation that transcends the mechanisms of origin specification. The population-averaged efficiency of replication origin usage changes during S phase in a strikingly similar manner in a highly diverse set of eukaryotes. The quantitative model previously proposed for origin activation in X. laevis can be generalized to explain this evolutionary conservation.
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19521533
???displayArticle.pmcLink???PMC2690853 ???displayArticle.link???PLoS One
Figure 1. I(t) in X. laevis, S. cerevisiae, S. pombe and D. melanogaster.A. I(t) in X. laevis. I(t) was determined from DNA combing data (open circles) as described in Materials and Methods in [26]. The data points were binned into 40 points and the dispersion in data value of each bin was determined (gray standard deviation bars). The red line is the best fit of the numerical model [26] to the data (Ï2â=â0.89). The values of free parameters as described in [26] are: P0â=â1.05Ã10â4±1.07Ã10â7 kbâ1 sâ1, P1â=â2.1Ã10â3±2Ã10â5 kbâ1 sâ1, Jâ=â5±0.5 sâ1 and N0â=â1000±3. B. I(t) in S. cerevisiae was determined from the replication timing profiles of Raghuraman et al. [3] as described in the Materials and Methods. C. I(t) in S. pombe. Only the 401 strong origins defined by Heichinger et al. [4] (blue circles) and 516 potential origins defined by Eshaghi et al. [5] (black triangles) were considered. D. I(t/tend) for D. melanogaster determined from replication timing profile of chromosome 2L [28].
Figure 2. I(t) in Homo sapiens.I(t) was determined from the replication timing profiles determined by Woodfine et al. [6], [7] for: (A) the whole genome, at 1 Mb resolution [7] or (B) chromosome 6, at 94 kb resolution [6], as described in the Materials and Methods.
Figure 3. Collapse of all I(t').All curves were shifted horizontally so that their starting points coincide with zero. The similarity distance (dsim) between the I(t') of other eukaryotes and the I(t') of X. laevis (Black) was measured using the Continuous Dynamic Time Warping method (see Material and Methods). By using the X. laevis data dispersion (gray error bars) we set the condition that if the measured distance between two curves is smaller than 0.94, the two curves are similar. In all cases we found dsim<0.94, therefore all I(t'), including the one generated by the numerical model, could be considered as similar. However, its possible to define a sequence of decreasing similarity between considered I(t') as: H. sapiens âs chromosome 6 (dsimâ=â0.27, Dark yellow)>D. melanogaster (dsimâ=â0.38, Orange)>numerical model (dsimâ=â0.41, Magenta)>S. pombe from Heichinger et al (dsimâ=â0.43, Olive)>H. sapiens (dsimâ=â0.44, Purple)>S. pombe from Eshaghi et al (dsimâ=â0.55, Blue)>S. cerevisiae (dsimâ=â0.85, Red).
Alexandrow,
Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation.
2005, Pubmed
Alexandrow,
Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation.
2005,
Pubmed
Alvino,
Replication in hydroxyurea: it's a matter of time.
2007,
Pubmed
Bechhoefer,
How Xenopus laevis replicates DNA reliably even though its origins of replication are located and initiated stochastically.
2007,
Pubmed
,
Xenbase
Czajkowsky,
DNA combing reveals intrinsic temporal disorder in the replication of yeast chromosome VI.
2008,
Pubmed
Dai,
DNA replication origins in the Schizosaccharomyces pombe genome.
2005,
Pubmed
Eshaghi,
Global profiling of DNA replication timing and efficiency reveals that efficient replication/firing occurs late during S-phase in S. pombe.
2007,
Pubmed
Gauthier,
Control of DNA replication by anomalous reaction-diffusion kinetics.
2009,
Pubmed
,
Xenbase
Gilbert,
In search of the holy replicator.
2004,
Pubmed
Goldar,
A dynamic stochastic model for DNA replication initiation in early embryos.
2008,
Pubmed
,
Xenbase
Hamlin,
A revisionist replicon model for higher eukaryotic genomes.
2008,
Pubmed
Heichinger,
Genome-wide characterization of fission yeast DNA replication origins.
2006,
Pubmed
Herrick,
Kinetic model of DNA replication in eukaryotic organisms.
2002,
Pubmed
,
Xenbase
Herrick,
Replication fork density increases during DNA synthesis in X. laevis egg extracts.
2000,
Pubmed
,
Xenbase
Hyrien,
Plasmid replication in Xenopus eggs and egg extracts: a 2D gel electrophoretic analysis.
1992,
Pubmed
,
Xenbase
Hyrien,
Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem.
2003,
Pubmed
Hyrien,
Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos.
1993,
Pubmed
,
Xenbase
Krasinska,
Cdk1 and Cdk2 activity levels determine the efficiency of replication origin firing in Xenopus.
2008,
Pubmed
,
Xenbase
Labit,
DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts.
2008,
Pubmed
,
Xenbase
Laskey,
Chromosome replication in early development of Xenopus laevis.
1985,
Pubmed
,
Xenbase
Lucas,
Mechanisms ensuring rapid and complete DNA replication despite random initiation in Xenopus early embryos.
2000,
Pubmed
,
Xenbase
Lygeros,
Stochastic hybrid modeling of DNA replication across a complete genome.
2008,
Pubmed
MacAlpine,
Coordination of replication and transcription along a Drosophila chromosome.
2004,
Pubmed
Mahbubani,
DNA replication initiates at multiple sites on plasmid DNA in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase
Marheineke,
Aphidicolin triggers a block to replication origin firing in Xenopus egg extracts.
2001,
Pubmed
,
Xenbase
Marheineke,
Control of replication origin density and firing time in Xenopus egg extracts: role of a caffeine-sensitive, ATR-dependent checkpoint.
2004,
Pubmed
,
Xenbase
McCune,
The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.
2008,
Pubmed
Nougarède,
Hierarchy of S-phase-promoting factors: yeast Dbf4-Cdc7 kinase requires prior S-phase cyclin-dependent kinase activation.
2000,
Pubmed
Patel,
DNA replication origins fire stochastically in fission yeast.
2006,
Pubmed
Patel,
The Hsk1(Cdc7) replication kinase regulates origin efficiency.
2008,
Pubmed
Raghuraman,
Replication dynamics of the yeast genome.
2001,
Pubmed
Rhind,
DNA replication timing: random thoughts about origin firing.
2006,
Pubmed
Schwaiger,
A question of timing: emerging links between transcription and replication.
2006,
Pubmed
Spiesser,
A model for the spatiotemporal organization of DNA replication in Saccharomyces cerevisiae.
2009,
Pubmed
Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase
Woodfine,
Replication timing of the human genome.
2004,
Pubmed
Woodfine,
Replication timing of human chromosome 6.
2005,
Pubmed
Yang,
How Xenopus laevis embryos replicate reliably: investigating the random-completion problem.
2008,
Pubmed
,
Xenbase
Zhang,
Reconstructing DNA replication kinetics from small DNA fragments.
2006,
Pubmed
